Childhood acute lymphoblastic leukemia (ALL) is the most common childhood cancer, accounting for almost one-quarter of childhood cancer survivors. We and others have demonstrated that ALL survivors develop a deleterious cardiometabolic phenotype following cancer therapy including: obesity (and sarcopenia), insulin resistance, chronically elevated c- reactive protein levels, dyslipidemia (especially increases in small, dense highly atherogenic LDL), hypertension, stroke, and ultimately an increased risk for cardiovascular death. The recognized causes of this adverse metabolic profile include: unhealthy diet, a sedentary lifestyle, reduced cardiorespiratory fitness, altered leptin:adiponecti metabolism, and decreased muscle strength and coordination directly and indirectly attributable to the cancer therapy. While those treated with cranial radiotherapy (CRT) are at the highest risk, all ALL survivors have an excess risk compared with individuals without a history of cancer. While treatment exposures are not modifiable, evidence suggests that ALL survivors may be able to ameliorate their cardiovascular risk through improvements in diet and physical activity. A 2008 study by Robien et al. evaluated 72 ALL survivors from the Childhood Cancer Survivor Study (CCSS) and found poor adherence to dietary guidelines. In a separate population of ALL survivors, we reported an association between unhealthy diet and increased visceral adiposity, higher systolic and diastolic blood pressure, greater waist circumference, and increased body mass index; small improvements in diet appeared to be metabolically beneficial. Therefore, methods to promote weight loss and increase levels of physical activity are urgently needed to mitigate the progression of this deleterious cardiometabolic phenotype. A landmark study by Appel, Clark, and colleagues, published in the New England Journal of Medicine in 2011, demonstrated that significant weight loss could be achieved entirely through phone- and web- based support, compared to self-directed weight loss via printed materials and a static web page, among obese community-dwelling adults. In this study, Exercise and Quality diet After Leukemia (EQUAL), we will test the effectiveness of a remotely-delivered diet and physical activity intervention, compared to self-directed weight loss, on the deleterious cardiometabolic phenotype observed among ALL survivors. Participants (200 CRT, 200 no CRT) will be a nationwide sample of ALL survivors enrolled in the CCSS. While CRT is an important risk factor for cardiovascular disease, and thus requires consideration among long-term survivors, the contemporary use of CRT is limited. Concurrent with the decline in use of CRT over the past 35 years, the prevalence of childhood obesity has increased dramatically. Today, many children are obese at the time of diagnosis, and so remain at risk for becoming obese long-term survivors despite non-irradiating therapies. Hence, a diet and physical activity intervention for weight loss is critically important for obese ALL survivors, regardless of whether they were treated with CRT. The EQUAL study brings together a research team with the necessary expertise and experience in obesity among adult survivors of childhood leukemia and in successful diet and physical activity interventions. This will be the first large scale weight loss study among childhood cancer survivors.